US4789744A - Process for the resolution of enantiomeric aryloxyphenoxy propionates - Google Patents
Process for the resolution of enantiomeric aryloxyphenoxy propionates Download PDFInfo
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- US4789744A US4789744A US07/081,518 US8151887A US4789744A US 4789744 A US4789744 A US 4789744A US 8151887 A US8151887 A US 8151887A US 4789744 A US4789744 A US 4789744A
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- United States
- Prior art keywords
- terpene
- aryloxyphenoxy
- esters
- menthol
- propionic acid
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- 238000000034 method Methods 0.000 title claims abstract description 15
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 title claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 18
- -1 terpene esters Chemical class 0.000 claims abstract description 17
- 235000019260 propionic acid Nutrition 0.000 claims abstract description 16
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 235000007586 terpenes Nutrition 0.000 claims abstract description 12
- WUOACPNHFRMFPN-UHFFFAOYSA-N alpha-terpineol Chemical compound CC1=CCC(C(C)(C)O)CC1 WUOACPNHFRMFPN-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 9
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 claims description 8
- 239000003480 eluent Substances 0.000 claims description 8
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 7
- NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- 238000010828 elution Methods 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 150000004672 propanoic acids Chemical class 0.000 abstract description 7
- 238000004811 liquid chromatography Methods 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000000926 separation method Methods 0.000 description 9
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 5
- 230000002363 herbicidal effect Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 4
- BDBJONVXJIXDSV-MRVPVSSYSA-N (2r)-2-[4-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxyphenoxy]propanoic acid Chemical compound C1=CC(O[C@H](C)C(O)=O)=CC=C1OC1=NC=C(C(F)(F)F)C=C1F BDBJONVXJIXDSV-MRVPVSSYSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- NOOLISFMXDJSKH-BBBLOLIVSA-N (1s,2r,5r)-5-methyl-2-propan-2-ylcyclohexan-1-ol Chemical compound CC(C)[C@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-BBBLOLIVSA-N 0.000 description 2
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 2
- BDBJONVXJIXDSV-UHFFFAOYSA-N 2-[4-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxyphenoxy]propanoic acid Chemical compound C1=CC(OC(C)C(O)=O)=CC=C1OC1=NC=C(C(F)(F)F)C=C1F BDBJONVXJIXDSV-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- REPVLJRCJUVQFA-KZVJFYERSA-N (1r,3s,4s,5s)-4,6,6-trimethylbicyclo[3.1.1]heptan-3-ol Chemical compound C1[C@H](O)[C@@H](C)[C@H]2C(C)(C)[C@@H]1C2 REPVLJRCJUVQFA-KZVJFYERSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- 101150108015 STR6 gene Proteins 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000006226 butoxyethyl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A process for the effective analytical or preparative resolution of the enantiomers of 2-(4-aryloxyphenoxy)propionic acids or the C1 -C4 alkyl esters thereof which comprises converting a racemic or partially resolved mixture of said 2-(4-aryloxyphenoxy)propionic acids or the C1 -C4 alkyl esters thereof to a pair of diastereomeric terpene esters by reaction with an optically active terpene alcohol and separating the diastereomers of the terpene ester by liquid chromatography with a silica column.
Description
The herbicidal activity of aryloxyphenoxy propionic acids and derivatives thereof is well known in the art. Furthermore, optical isomers are often known to exhibit enhanced herbicidal activity over the corresponding racemates. For example, U.S. Pat. No. 4,531,969 has disclosed that the R-enantiomers of certain 2-(4-aryloxyphenoxy)propionic acids and certain derivatives thereof are distinguished by a considerably enhanced herbicidal action compared to the racemic modifications. Since reduced quantities of herbicide are required to achieve comparable levels of control, the application of mixtures enriched in the more efficacious R-enantiomer offers both economical and environmental advantages.
To exploit the agrinomic benefits of these advantages, it is necessary to efficiently resolve the racemic mixtures of the herbicides that are normally produced industrially and to accurately determine the ratio of the R- and S-enantiomers in the resulting composition.
Various methods for obtaining high concentrations of individual enantiomers are known. The most common method of resolution of a racemic modification involves its conversion by an optically active reagent into a mixture of diastereomers which can then be separated on the basis of their different physical properties. Diastereomers are generally separated by fractional crystallization, though occasionally by fractional distillation or chromatography. Once the diastereomers have been separated, they can be reconverted to the individual enantiomers and the optically active resolving agent can be recovered.
Unfortunately, the differences in physical properties of the diastereomers are rarely if ever great enough to effect a total separation with one crystallization. Usually repeated crystallizations must be used and the process is long and tedious. The same situation generally applies to differential boiling points and differential absorption with respect to distillation and chromatographic separations.
The present invention provides a process for the effective analytical or preparative resolution of the enantiomers of 2-(4-aryloxyphenoxy)propionic acids of formula (I) ##STR1## wherein Ar is ##STR2## and X is CF3, F, Cl, Br or I and Y is H, F, Cl, Br or I
or the C1 -C4 alkyl esters thereof which comprises converting a racemic or partially resolved mixture of said 2-(4-aryloxyphenoxy)propionic acid or C1 -C4 alkyl ester thereof to a pair of diastereomeric terpene esters by reaction with an optically active terpene alcohol and separating the diastereomers of the terpene ester by liquid chromatography with a silica column. After separation the individual enantiomers of (I) can be recovered by hydrolysis of the separated terpene ester diastereomers.
This procedure allows the efficient separation of the enantiomers of 2-(4-aryloxyphenoxy)propionic acids to produce high optical purity materials of greater herbicidal activity than the unresolved racemates. Additionally, the method is useful for the accurate determination of the enantiomeric content of commercial compositions.
Any naturally occurring, optically active terpene alcohol is contemplated as the resolving agent. Relatively inexpensive d-menthol and l-menthol are the preferred embodiments.
The diastereomeric terpene esters to be separated can be prepared by a variety of methods, either with or without a solvent. However, it is important that the chosen methods do not cause racemization of the chiral center. For example, the racemic or partially resolved 2-(4-aryloxyphenoxy)propionic acid (I) can be treated with excess thionyl chloride to form the acid chloride. Removal of excess thionyl chloride followed by reaction of the acid chloride at elevated temperatures with a terpene alcohol, for example, d-menthol or l-menthol, provides a product consisting of a pair of diastereomeric esters. Alternatively, the 2-(4-aryloxyphenoxy)propionic acid (I) can be directly esterified with the terpene alcohol by standard procedures, preferably in the presence of a dehydrating agent such as 2,2-dimethoxypropane.
Similarly, the C1 -C4 alkyl esters of 2-(4-aryloxyphenoxy)propionic acids (I) can be transesterified with the terpene alcohol by conventional techniques. Alternatively, the esters can be initially hydrolyzed to the acid which can be further converted to the diastereomeric terpene esters as described hereinabove.
The pair of diastereomeric terpene esters can be separated on a silica liquid chromatographic column. Silica is advantageously employed because it is relatively inexpensive and stable. The silica particle size may vary from 1 to 500μ. Particle sizes of from 5 to 150μ are preferred. Best resolutions are obtained by using particles of a narrow range, for example, less than ±10μ.
The column size is limited only by mechanical considerations. Those skilled in the art will appreciate the limitations on column size imposed by the scale of the operation. In general, the diastereomer weight load into the chromatographic system is limited by the capacity of the silica packing. More loading results in less resolution.
The eluents employed are simple and non-optically active. As is well known to those skilled in the art, the choice of eluents greatly affects the separation. Various components and concentrations of these components can be used. The optimal choice of eluent is dictated by the compounds to be separated and the column characteristics. Mixtures of hydrocarbons and halogenated hydrocarbons are preferred to achieve the desired separation.
Various eluent flow rates can be used limited by the pressure limitations of the chromatographic system. Optimum flow rates can be readily determined by procedures well known to those skilled in the art.
After the diastereomeric terpene esters have been separated, hydrolysis of the individual esters provides both the R- and S-enantiomers of exceedingly high optical purity. The more herbicidally active R-2-(4-aryloxyphenoxy)propionic acid may be esterified using conventional ester formation procedures to produce agriculturally acceptable esters which include the following: methyl, ethyl, propyl, butyl, octyl, ethoxyethyl, butoxyethyl and methoxypropyl.
The less herbicidally active S-enantiomer is preferably racemized by heating in the presence of a strong base and recycling the resulting racemate to the separation process.
The following examples illustrate the invention.
A racemic mixture of 2-(4-((3-fluoro-5-trifluoromethyl-2-pyridinyl)oxy)phenoxy)propionic acid was treated with an excess of thionyl chloride at 55° C. to form the acid chloride. Excess thionyl chloride was removed and a 5 mole percent excess of l-menthol was added and the mixture was heated at 55° C. for 2 hours with stirring. The product, which consisted of a pair of diastereomeric l-menthol esters, was dissolved in methylene chloride and injected into a preparative liquid chromatographic system.
INJECTION: 100 mg (milligrams) 2-(4-((3-fluoro-5-trifluoromethyl-2-pyridinyl)oxy)phenoxy)propionic acid, l-menthol ester diastereomers.
COLUMN: 1 m (meter)×4.6 mm (millimeter) ID packed with 30μ particle size, 60 Å pore size, 500-550 m2 /g surface area silica (supplied by Sigma Chemical).
ELUENT: 20 percent (1/2 water saturated) ethylene dichloride; 80 percent hexane (v/v).
FLOW RATE: 2.0 mL/min
DETECTION: UV 280 nm
The cuts were collected at varying intervals of one to several minutes. Since flow rate was 2.0 mL/min, time of collection is easily ascertained from the cumulative volume data in Table I. The collected cuts were analyzed for enantiomer composition.
TABLE I ______________________________________ Cumulative % R, of % S, of Volume, mL R/S Ratio Total R Total S ______________________________________ 0-74 -- 0 0 74-88 100/0 53.0 0 88-92 95.8/4.2 12.6 0.5 92-97 47.4/52.6 8.0 8.8 97-102 36.1/63.9 5.7 10.0 102-108 33.7/66.3 5.1 10.0 108-116 31.2/68.8 5.7 12.4 116-126 26.9/73.1 4.8 13.0 126-136 21.2/78.8 3.0 11.0 136-146 13.2/86.8 1.4 9.0 146-158 4.0/96.0 0.4 9.4 158-170 1.0/99.0 0.08 7.4 170-194 0.9/99.1 0.07 7.3 194-220 3.9/96.1 0.04 1.0 ______________________________________
The R-form of the l-menthol ester of the propionic acid was isolated in a 65.6 percent yield. After hydrolysis, R-2-(4-((3-fluoro-5-trifluoromethyl-2-pyridinyl)oxy)phenoxy)propionic acid of at least 99.7 percent R configuration was obtained.
Similar results were achieved using d-menthol, in which case the order of elution of the R- and S-forms was reversed.
Example 1 was repeated except that 50 mg of sample instead of 100 mg were injected. The results are summarized in Table II.
TABLE II ______________________________________ Cumulative % R, of % S, of Volume, mL R/S Ratio Total R Total S ______________________________________ 0-92 -- 0 0 92-114 100/0 72.2 0 114-118 98.6/1.4 11.1 0.16 118-122 48.6/51.4 6.0 6.2 122-128 24.1/75.9 4.5 14.0 128-134 19.4/80.6 3.1 12.5 134-140 13.6/86.4 1.8 11.4 140-148 6.9/93.1 1.0 13.6 148-158 2.0/98.0 0.31 15.3 158-220 0/100 0 26.8 ______________________________________
The R-form of the l-menthol ester of the propionic acid was isolated in an 83.3 percent yield. After hydrolysis, R-2-(4-((3-fluoro-5-trifluoromethyl-2-pyridinyl)oxy)phenoxy)propionic acid of at least 99.9 percent R configuration was obtained.
Example 1 was repeated except that a 30μ, 100 Å column was used and the eluent was changed to 20 percent ethylene dichloride/80 percent hexane absent 1/2 water saturation. The results are summarized in Table III.
TABLE III ______________________________________ Cumulative % R, of % S, of Volume, mL R/S Ratio Total R Total S ______________________________________ 0-48 -- 0 0 48-62 100/0 49.4 0 62-67 62.0/38.0 13.8 8.6 67-73 40.1/59.9 9.3 14.3 73-79 37.7/62.3 7.3 12.3 79-83 35.3/64.7 5.7 10.6 83-91 32.7/67.3 4.5 9.4 91-97 38.8/61.2 5.3 8.6 97-103 25.1/74.9 2.2 6.7 103-109 19.7/80.3 1.4 5.9 109-115 10.3/89.7 0.6 5.6 115-121 6.2/93.8 0.3 4.4 121-127 2.9/97.1 0.1 3.8 127-137 2.0/98.0 0.1 5.2 137-160 1.2/98.8 0.05 4.6 160-184 0/100 0 0.1 ______________________________________
The following separations (Table IV), expressed as α where α=(T2 -T0)/(T1 -T0) were obtained. T2 is the retention time of the second diastereomer eluted. T1 is the retention time of the first diastereomer eluted. T0 is the retention time of unretained component. These separations were obtained using a 25 cm×4.6 mm ID, 5μ particle size silica column and a 2 mL/min flow rate of 20 percent ethylene dichloride/80 percent hexane (V/V eluent).
TABLE IV
______________________________________
Chromatographic Resolutions of
##STR3##
Ar Terpene Alcohol
α
______________________________________
##STR4## 1-menthol 1.20
##STR5## d-menthol 1.19
##STR6## (+)-isopinocampheol
1.06
##STR7## (+)-isomenthol 1.10
##STR8## 1-menthol 1.18
##STR9## 1-menthol 1.12
______________________________________
Various modifications may be made in the present invention without departing from the spirit or scope thereof, and it is understood that I limit myself only as defined in the appended claims.
Claims (3)
1. A process for the resolution of the enantiomers of a 2-(4-aryloxyphenoxy)propionic acid of the formula ##STR10## wherein Ar is ##STR11## and X is CF3, F, Cl, Br or I and Y is H, F, Cl, Br or I
or a C1 -C4 alkyl ester thereof which comprises converting a racemic or partially resolved mixture of said 2-(4-aryloxyphenoxy)propionic acid or C1 -C4 alkyl ester thereof to a pair of diastereomeric terpene esters by reaction with an optically active terpene alcohol and separating the diastereomers of the terpene esters by elution from a silica column with an eluent selected from the group consisting of hydrocarbons, halogenated hydrocarbons, water-saturated halogenated hydrocarbons and mixtures thereof.
2. The process of claim 1 wherein the optically active terpene alcohol is d-menthol or l-menthol.
3. The process of claim 1 wherein the individual enantiomers of the 2-(4-aryloxyphenoxy)propionic acid are recovered by hydrolysis of the separated terpene ester diastereomers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/081,518 US4789744A (en) | 1987-08-05 | 1987-08-05 | Process for the resolution of enantiomeric aryloxyphenoxy propionates |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/081,518 US4789744A (en) | 1987-08-05 | 1987-08-05 | Process for the resolution of enantiomeric aryloxyphenoxy propionates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US4789744A true US4789744A (en) | 1988-12-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US07/081,518 Expired - Fee Related US4789744A (en) | 1987-08-05 | 1987-08-05 | Process for the resolution of enantiomeric aryloxyphenoxy propionates |
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| Country | Link |
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| US (1) | US4789744A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5288251A (en) * | 1991-12-25 | 1994-02-22 | Sumitomo Wiring Systems, Ltd. | Connector |
| US20180207085A1 (en) * | 2015-07-15 | 2018-07-26 | Bakel Srl | Cosmetic composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4531969A (en) * | 1977-12-24 | 1985-07-30 | Hoechst Aktiengesellschaft | Herbicidal esters of D-1-(phenoxy-4-phenoxy)propionic acid |
-
1987
- 1987-08-05 US US07/081,518 patent/US4789744A/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4531969A (en) * | 1977-12-24 | 1985-07-30 | Hoechst Aktiengesellschaft | Herbicidal esters of D-1-(phenoxy-4-phenoxy)propionic acid |
Non-Patent Citations (9)
| Title |
|---|
| Guyon et al., J. Chromatography, 152, pp. 551 556, (1978). * |
| Guyon et al., J. Chromatography, 152, pp. 551-556, (1978). |
| Jiang et al., J. Chromatography, 248, pp. 143 149, (1982). * |
| Jiang et al., J. Chromatography, 248, pp. 143-149, (1982). |
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| US5288251A (en) * | 1991-12-25 | 1994-02-22 | Sumitomo Wiring Systems, Ltd. | Connector |
| US20180207085A1 (en) * | 2015-07-15 | 2018-07-26 | Bakel Srl | Cosmetic composition |
| US11013681B2 (en) * | 2015-07-15 | 2021-05-25 | Bakel Srl | Cosmetic composition |
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